The αE-catenin protein, a component of the epithelial cadherin-catenin adhesion complex, is a well-known invasion suppressor. To reach full functionality of the cadherin-catenin cell-cell adhesion complex, it is necessary to link the complex to the actin cytoskeleton. AlphaE-catenin provides this link by binding to β-catenin or plakoglobin through its amino terminal side, and by binding actin or the actin-binding molecule α-actinin through its carboxy-terminus (reviewed in Rudiger, 1998). It has been shown that loss of αE-catenin affects cell-cell adhesion and promotes tumorigenicity (Ewing et al., 1995). In many cases of invasive cells, αE-catenin defects are seen, and introduction of exogenous α-catenin can restore cell-cell aggregation and counteract invasiveness (Hirano et-al., 1992; van Hengel et al., 1997; Watabe et al., 1994).
The family of α-catenins contains so far four known members. The αE-catenin protein is ubiquitously expressed, mainly in epithelial tissues. AlphaN-catenin protein has about 75% identity to αE-catenin, but is restricted in its expression to neural tissues (Hirano et al., 1992). In analogy with αE-catenin, it can also bind to β-catenin and plakoglobin and is supposed to bind α-actinin and actin. Although the vinculin protein shows much less identity (20%) to αE- and αN-catenin, it shares some similar characteristics. This protein is mainly found in focal adhesions where it forms the link to the actin cytoskeleton and binds the integrin-binding molecule talin. Vinculin is sometimes found in cell-cell contacts as well, and it may even be able to take over the function of αE-catenin, by binding to β-catenin (Hazan et al., 1997). On the other hand, vinculin has been reported to bind to a central region of αE-catenin and to be essential for apical junctional organization (Watabe-Uchida et al., 1998). Moreover, vinculin has a unique proline-rich hinge domain, which is absent in the other family members and which allows the vinculin tail to bind to the head, thus masking some “cryptic” binding sites (Johnson & Craig, 1995). For the recently reported α-catulin (Janssens et al., 1999; Zhang et al., 1998), the identity to other family members is about 25% at the amino acid level, but no functional evidence for adhesive properties was found yet. In addition to their structural role, it is becoming clear that α-catenins and vinculin also have a regulatory function in the coordination of assembly and disassembly of junctions (Rudiger, 1998), and that αN-catenin can locate to the nucleus where it inhibits β-catenin/Tcf signaling (Giannini et al., 2000).